Ursodeoxycholic acid is also known as Ursodiol and the abbreviation UDCA, is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria.
Formula - C24H40O4
Mol. mass - 392.56 g/mol
Primary bile acids are produced by the liver and stored in the gall bladder. When secreted into the intestine, primary bile acids can be metabolized into secondary bile acids by intestinal bacteria. Primary and secondary bile acids help the body digest fats. Ursodeoxycholic acid helps regulate cholesterol by reducing the rate at which the intestine absorbs cholesterol molecules while breaking up micelles containing cholesterol. Because of this property, ursodeoxycholic acid is used to treat (cholesterol) gallstones non-surgically.
While some bile acids are known to be colon tumor promoters (e.g. deoxycholic acid), others such as ursodeoxycholic acid are thought to be chemopreventive, perhaps by inducing cellular differentiation and/or cellular senescence in colon epithelial cells.
It is believed to inhibit apoptosis.
Ursodeoxycholic acid has also been shown experimentally to suppress immune response such as immune cell phagocytosis. Prolonged exposure and/or increased quantities of systemic (throughout the body, not just in the digestive system) ursodeoxycholic acid can be toxic.
Ursodeoxycholic acid is marketed under the trade names Actigall, Ursosan, Ursofalk, BILIVER, Egyurso, Urso, Urso Forte, Deursil and Coric.
Ursodeoxycholic acid can be chemically synthesized and was brought to market by the Montreal-based Axcan Pharma in 1998, which continues to market the drug.
The drug reduces cholesterol absorption and is used to dissolve (cholesterol) gallstones in patients who want an alternative to surgery. The drug is very expensive, however, and if the patient stops taking it, the gallstones tend to recur if the condition that gave rise to their formation does not change. For these reasons, it has not supplanted surgical treatment by cholecystectomy.
It is the only FDA approved drug to treat primary biliary cirrhosis.
A Cochrane review to evaluate if ursodeoxycholic acid has any beneficial effect in primary biliary cirrhosis patients included 16 randomized clinical trials with a total of 1447 patients. The primary outcome measures were mortality and mortality or liver transplantation. Although treatment with ursodeoxycholic acid showed a reduction in liver biochemistry, jaundice, and ascites, it did not decrease mortality or liver transplantation.
In absence of biochemical response to 13-15mg/kg/day ursodeoxycholic acid, its use is associated with an incidence of 20% hepatocellular carcinoma in patients with primary biliary cirrhosis in 15 years.
In children, its use is not licensed, as its safety and effectiveness are not established.
In double the recommended daily dose ursodeoxycholic acid reduces elevated liver enzyme levels in patients with primary sclerosing cholangitis, but its use was associated with an increased risk of serious adverse events (the development of cirrhosis, varices, death or liver transplantation) in patients who received ursodeoxycholic acid compared with those who received placebo). After adjustment for baseline stratification characteristics, the risk was 2.1 times greater for death,transplantation, or minimal listing criteria in patients on ursodeoxycholic acid than for those on placebo (P = 0.038). Serious adverse events, were more common in the ursodeoxycholic acid group than the placebo group
Research by the Imperial College London has produced promising results in the treatment of arrhythmia, both in patients who have suffered a heart attack and in foetuses, by using ursodiol to change the electrical properties of myofibroblast cells. Myofibroblasts disrupt the transmission of electrical signals controlling heart rhythm.
The drug is generally not derived from animals.However, it is believed up to 10,000 bile bears are kept on farms in China, Vietnam and South Korea for the purpose of harvesting ursodeoxycholic acid. Ursodeoxycholic acid is found in large quantities in bear bile.
Indication & Dosage
Dissolution of cholesterol-rich gallstones
Adult: 6-12 mg/kg daily as a single dose at bedtime or in 2-3 divided doses continued for 3-4 mth after radiological disappearance of stones. Doses may be divided unequally with a higher dose given before bedtime to counteract increase in biliary cholesterol saturation which occurs in early morning. Max: 15 mg/kg.
Hepatic impairment:Chronic liver disease (except primary biliary cirrhosis): use with caution.
Primary biliary cirrhosis
Adult: 10-15 mg/kg daily in 2-4 divided doses.
Prophylaxis of gallstones in patients undergoing rapid weight loss
Adult: 300 mg bid.
Hepatic impairment: Chronic liver disease (except primary biliary cirrhosis): use with caution.
Cholestyramine, charcoal and antacids may reduce effectiveness. Aluminum-based antacids may reduce absorption. Oestrogens and clofibrate may counteract effectiveness of ursodeoxycholic acid by increasing cholesterol elimination in bile. Possible increase in ciclosporin serum concentration. Decreased effectiveness of dapsone. Possible decrease in serum ciprofloxacin and nitrendipine.
Mechanism of Action
Ursodeoxycholic acid suppresses hepatic synthesis and secretion of cholesterol and also inhibits intestinal absorption of cholesterol.
Absorption: Rapidly and completely absorbed from the GI tract.
Distribution:Protein binding: 96-98%. Undergoes enterohepatic recycling.
Metabolism:Partly conjugated in the liver before being excreted into the bile. Free and conjugated forms undergo 7a-dehydroxylation to lithocholic acid under the influence of gut bactera. Some are reabsorbed and then further conjugated and sulfated by the liver.
Acido Ursodesossicolico Actavis
Actavis Italy, Italy
Acido Ursodesossicolico Angenerico
Acido Ursodesossicolico Doc
DOC Generici, Italy
Acido Ursodesossicolico Dorom
Acido Ursodesossicolico EG
Acido Ursodesossicolico Mylan
Acido Ursodesossicolico ratiopharm
ratiopharm Italia, Italy
Acido Ursodesossicolico Winthrop
Winthrop Ph.Italia, Italy
Novartis, New Zealand; Watson, United States
Bilenor (Ursodeoxycholic Acid and Chenodeoxycholic Acid)
Myung Moon, South Korea
Dr Falk, Spain
AC Farma, Peru
Norgine, United Kingdom; Sanofi-Aventis, Portugal
De-ursil RR mite
Francia Farmaceutici, Italy
Chin Teng, Taiwan
TTY Biopharm, Taiwan
Lithofalk (Ursodeoxycholic Acid and Chenodeoxycholic Acid)
Tatsumi Kagaku, Japan
Fuso Pharmaceutical, Japan
Chen Ho, Taiwan
Newai Chem, Taiwan
Medisa Shinyaku, Japan
Win-Medicare, India; Win-Medicare, Thailand
Swiss Pharm, Taiwan
Darya-Varia, Indonesia; Falk, Indonesia
Taiyo Pharmaceutical, Japan
Errekappa Euroterapici, Italy
Towa Yakuhin, Japan
Towa Yakuhin, Japan
CP, Malta; Wockhardt, United Kingdom
Dr. Falk, Portugal
Dae Woong, South Korea; Daewoong, Thailand
Zambon, Brazil; Zambon, Colombia; Zambon Italia, Italy
Aptalis, United States
Aptalis, United States; Axcan, Canada; Mitsubishi Tanabe Pharma, Hong Kong; Mitsubishi-Tokyo, Taiwan; Tanabe Mitsubishi Pharma, Japan
ABC Farmaceutici, Georgia; ABC Farmaceutici, Italy
ABL Pharma, Peru
Zambon, Belgium; Zambon, Switzerland; Zambon, Germany; Zambon, Spain; Zambon, Indonesia; Zambon, Netherlands
Ta Fong, Taiwan
Ursodeoxycholic acid Zensei
Zensei Yakuhin, Japan
Ursodeoxycholic Acid-Daewoong Pharm
Daewoong Pharmaceutial Co. Ltd, China
Ursodeoxycholic Acid-Sunve Pharm
Ying Yuan, Taiwan
General Pharma, Bangladesh
CorePharma, United States
Ursodiol Epic Pharma
Epic Pharma, United States
Glenmark, United States
Lannett, United States
Mylan, United States
Ursodiol RR Zentiva
Teva, United States
Watson, United States
Farmasa, Mexico; ARIS, Turkey; Biotoscana, Chile; Biotoscana, Colombia; Biotoscana, Peru; Cevallos, Argentina; Codali, Belgium; Codali, Luxembourg; Dr Falk, Hong Kong; Dr. Falk, Israel; Dr. Falk, Norway; Dr. Falk, Russian Federation; Dr. Falk Pharma, Czech Republic; Dr. Falk Pharma, Serbia; Eureco, Netherlands; Falk, Bosnia & Herzegowina; Falk, China; Falk, Germany; Falk, United Kingdom; Falk, Hungary; Falk, Ireland; Falk, Lithuania; Falk, Malta; Falk, Philippines; Falk, Poland; Falk, Romania; Falk, Singapore; Falk, Slovakia; Falk, Thailand; Falk Pharma GmbH, Latvia; Farmak, Estonia; Galenica, Greece; IFET, Greece; Meda, Sweden; Merck, Austria; Orphan, Australia; Salus, Slovenia; Schwabe, Costa Rica; Schwabe, Guatemala; Schwabe, Honduras; Schwabe, Panama; Schwabe, El Salvador; Tramedico, Netherlands; Vifor, Switzerland; Würth, Croatia (Hrvatska); Zydus Cadila, India
So.Se. Pharm, Italy
Galen, United Kingdom
Siu Guan, Taiwan
Gentle, Taiwan; Guardian Pharmatama, Indonesia
Evolan, Sweden; Pro.Med.CS, Bosnia & Herzegowina; Pro.Med.CS, Czech Republic; Pro.Med.CS, Estonia; Pro.Med.CS, Georgia; Pro.Med.CS, Lithuania; Pro.Med.CS, Romania; Pro.Med.CS, Serbia; Pro.Med.CS, Slovenia; Pro.Med.CS, Slovakia
Sanofi-Aventis, South Africa
Shyh Dar, Taiwan